NM_001872.5:c.314A>G

Variant names:

• chr13-46082511-T-C
• NM_001872.5:c.314A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001872.5(CPB2):​c.314A>G​(p.Gln105Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CPB2 NM_001872.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.39
• Publications: 0 publications found

Genes affected

CPB2 (HGNC:2300): (carboxypeptidase B2) Carboxypeptidases are enzymes that hydrolyze C-terminal peptide bonds. The carboxypeptidase family includes metallo-, serine, and cysteine carboxypeptidases. According to their substrate specificity, these enzymes are referred to as carboxypeptidase A (cleaving aliphatic residues) or carboxypeptidase B (cleaving basic amino residues). The protein encoded by this gene is activated by trypsin and acts on carboxypeptidase B substrates. After thrombin activation, the mature protein downregulates fibrinolysis. Polymorphisms have been described for this gene and its promoter region. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jun 2013]

CPB2-AS1 (HGNC:39898): (CPB2 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001872.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPB2	NM_001872.5	MANE Select	c.314A>G	p.Gln105Arg	missense	Exon 4 of 11	NP_001863.3	Q96IY4-1
	CPB2	NM_001278541.2		c.314A>G	p.Gln105Arg	missense	Exon 4 of 10	NP_001265470.1	A0A087WSY5
	CPB2-AS1	NR_046226.1		n.119-12342T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPB2	ENST00000181383.10	TSL:1 MANE Select	c.314A>G	p.Gln105Arg	missense	Exon 4 of 11	ENSP00000181383.4	Q96IY4-1
	CPB2	ENST00000882332.1		c.416A>G	p.Gln139Arg	missense	Exon 4 of 11	ENSP00000552391.1
	CPB2	ENST00000882315.1		c.362A>G	p.Gln121Arg	missense	Exon 4 of 11	ENSP00000552374.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		6.4
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.52
MutPred		0.56		Gain of catalytic residue at Q105 (P = 0.0334)
MVP		0.52
MPC		1.2
ClinPred		0.98	D
GERP RS		5.7
Varity_R		0.86
gMVP		0.84
Mutation Taster		=38/62	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr13-46656646;